Respiration monitoring system based on sensed blood pressure variations

ABSTRACT

A system and method obtains physiologic parameter information of an animal or human, such as respiratory rate, from a blood pressure signal from an implanted blood pressure sensor in the animal or human. Specifically, the blood pressure signal is externally signal processed to develop an amplitude versus time waveform. A sequence of selected blood pressure features derived from individual cardiac cycles of the amplitude versus time waveform over a selected time interval are extracted from the developed amplitude versus time waveform. A mathematical model is fitted to the extracted sequence of selected blood pressure features to yield a fitted mathematical model. The physiologic parameter information is computed from the fitted mathematical model.

CROSS REFERENCE TO RELATED APPLICATION(S)

This application is a continuation of U.S. Pat. application Ser. No.08/819,888, filed on Mar. 18, 1997, now U.S. Pat. No. 6,299,582 which inturn is a continuation of U.S. Pat. application Ser. No. 08/535,656,filed Sep. 28, 1995, now abandoned, the specifications of which areincorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to obtaining physiologicalparameters from animals or humans, and more particularly to a system forderiving respiratory related information from a blood pressure signalobtained from either humans or animals.

BACKGROUND OF THE INVENTION

In animals or humans, it is often desirable to be able to monitor avariety of physiological parameters for purposes of research,therapeutics, and diagnosis. One such parameter that is of value isrespiration. Simple measurement of the animal's or human's respirationrate have included the use of plethysmographs, strain gauges, chestimpedance measurements, diaphragmatic EMG measurements, and other knownmeasurement devices. For example in animal research, the plethysmographapproach requires the use of a non-compliant closed box in which theanimal is placed with a means for measuring either the air flow in andout of the box or pressure changes inside the box or air flow at theanimal's mouth when breathing air from outside or inside the closedcontainer. While plethysmographs work reasonably well with humansubjects who can cooperate with test personnel, it is unreliable whendealing with laboratory animals, such as rats, dogs, monkeys, and etc.

The use of strain gauges and apparatus for measuring chest impedancechanges generally require the animal to be tethered to the testequipment via electrical leads and the like. This does not lend itselfto chronic testing and, moreover, strain gauges are quite sensitive tomovement artifacts that can mask the desired signal output.Diaphragmatic EMG measurements can be used to determine respiratoryrate, but electrode placement requires a higher skilled surgeon, andelectrical noise from ECG and other sources can make accurate detectionof respiration difficult.

To allow for animal mobility, it has proven advantageous to surgicallyimplant sensors within the animal along with a telemetry transmitter sothat the sensed signals can be electronically transmitted to an externalreceiver without the need for exteriorized conductive leads orcatheters. U.S. Pat. No. 4,846,191 to Brockway, et al., owned byapplicant's assignee, describes an implantable blood pressure sensingand telemetering device suitable for long-term use in a variety oflaboratory animals. A solid-state pressure sensor is fluid coupled to aselected blood vessel and the signal produced by the sensor isamplified, digitized and transmitted, transcutaneously, to an externalreceiver by means of a battery-powered transmitter. Once the bloodpressure data are received, they are signal processed to recoverfeatures thereof, such as mean systolic pressure, mean diastolicpressure, mean arterial pressure, heart rate, etc. The Brockway et al.′191 patent also recognizes that the pressure sensing system usedtherein can be adapted to monitor intrathoracic pressure from whichrespiratory rate and other respiratory parameters can be derived.However, if it is desired to chronically monitor both blood pressure andrespiratory activity following the teachings of the Brockway et al.patent, plural sensors and at least one telemetry transmitter with amultiplexing capability is required

The Kahn et al. U.S. Pat. No. 4,860,759 demonstrates the combined use oftransthoracic impedance and strain gauge sensors to monitor respirationrate. The approach disclosed in the Kahn et al. patent suffers from manyshortcomings, not the least of which is the quality of the resultingdata.

An example of the use of multiple, chronically implanted sensors inlaboratory animals is described in R. Rubini et al., Power SpectrumAnalysis of Cardiovascular Variability Monitored By Telemetry inConscious, Unrestrained Rats, Journal of the Autonomic Nervous System,vol. 45, at 181-190 (1993). In the experiments described in the Rubiniet al. paper, telemetry equipment manufactured by Data SciencesInternational (applicant's assignee) was utilized. However, theexperimenters involved, while recognizing that a respiratory artifactwas present in the sensed blood pressure data, discarded this componentin favor of lower frequency components relating to sympatheticmodulation of the cardiovascular system.

It is also known in the art that blood pressure is influenced byrespiratory activity. In this regard, reference is made to H. Barthelmesand J. Eichmeier, A Device with Digital Display for the Determination ofRespiratory Frequency from the Respiratory Fluctuations of BloodPressure, Biomedizinische Technik, vol. 18, No. 4 (August 1973) and toD. Laude et. al., Effect of Breathing Pattern on Blood Pressure andHeart Rate Oscillations in Humans, Clinical and ExperimentalPharmacology and Physiology, vol. 20, at 619-626 (1993). A systemdescribed in the Barthelmes paper employs an analog electronic filter toextract respiration rate from blood pressure signals. In the Laudearticle, human subjects were told to breath in rhythm with a metronomeat several discrete frequencies while blood pressure was continuouslymeasured. This study led to the conclusion that the relationship betweensystolic blood pressure and respiration differs from that betweenrespiration and respiration sinus arrhythmia.

Although there are many studies in the published literature documentingvariations of blood pressure with respiration, there is a need for animproved method and apparatus to derive respiratory parameters fromblood pressure data.

SUMMARY OF THE INVENTION

The present invention provides a method and apparatus for obtainingphysiologic parameter information of an animal or human other than bloodpressure from a blood pressure signal indicative of sensed variations inblood pressure of the animal or human. The blood pressure signal isexternally signal processed to develop an amplitude versus timewaveform. A sequence of selected blood pressure features derived fromindividual cardiac cycles of the amplitude versus time waveform over aselected time interval are extracted from the developed amplitude versustime waveform. A mathematical model is fitted to the extracted sequenceof selected blood pressure features to yield a fitted mathematicalmodel. The physiologic parameter information is computed from the fittedmathematical model.

In a preferred embodiment of the present invention, the physiologicparameter information obtained is respiratory rate. In accordance withthis preferred embodiment, a catheter tip of a blood pressure sensor issurgically implanted in an animal's vascular system where the sensorprovides an electrical signal related to variations in the animal'sblood pressure. A telemetry transmitter, also implanted in the animal,is connected to the blood pressure sensor for selectively transmitting adigitized version of the sensed electrical signal to an externalreceiver. The external receiver receives the digitized version of thesensed electrical signal and provides the blood pressure signal. Theblood pressure signal is then signal processed in a digital computer todevelop the amplitude versus time waveform, which is in a digitizedform. The signal processing algorithm extracts from the digitizedamplitude versus time waveform the sequence of selected blood pressurefeatures such as beat-to-beat systolic data points, beat-to-beatdiastolic data points, or beat-to-beat mean values of blood pressureover a predetermined time interval.

The mathematical model in this preferred embodiment is an n^(th) orderpolynomial curve, which is preferably fitted to n+1 sequential points ofthe selected blood pressure features to obtain a fitted n^(th) orderpolynomial curve. The fitted n^(th) order polynomial curve preferablyincludes curve fit data values substantially equi-spaced in time. Thecurve fit data values are tested for critical points in accordance witha predetermined criteria such as a criteria relating peak values tozero-crossings of the fitted curve. Next, the computer determines fromthe critical points whether they are a maximum or a minimum whereby therespiratory rate can be determined from successive maximum and minimumcritical points.

In one alternative embodiment of the present invention, spectralanalysis is performed on the fitted mathematical model. In anotheralternative embodiment, several distinct blood pressure features foreach cardiac Cycle are combined to yield a sequence of averaged bloodpressure features, and the mathematical model is then fitted to theresulting sequence of averaged blood pressure features.

The implantable pressure sensor/transmitter described in the Brockway etal. ′191 patent referenced in the background section provides anexcellent means for monitoring blood pressure. By appropriately signalprocessing the telemetered blood pressure waveforms, respiration rateand other physiologic parameters can be derived therefrom according tothe present invention.

Accordingly, the present invention provides an improved system formonitoring a plurality of physiologic parameters in animals or humansusing a single implanted telemetric sensor. Moreover, the presentinvention provides a system for measuring blood pressure and respiratoryparameters in such animals or humans using a single telemetric sensor.The present invention also provides a system for extracting respiratoryrelated physiologic data from animals or humans using an implanted bloodpressure sensor and telemetry transmitter where the transmitted bloodpressure signal is externally signal processed to recover therespiratory information contained in the blood pressure signal. It isnot, however, necessary that the blood pressure data be telemetered. Ablood pressure sensor could be connected via wires to an amplifier andanalog-to-digital converter and then input into the computer-basedsystem according to the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a system block diagram of a system according to the presentinvention for collecting and processing blood pressure related signalsobtained from a plurality of lab animals to derive not onlycardiovascular data, but also respiratory information.

FIG. 2 is a software flow diagram illustrating the signal processingalgorithm executed by the computer shown in FIG. 1 whereby the length ofthe respiratory cycle and therefore respiratory rate is obtained.

FIG. 3 is a graph illustrating a plot of blood pressure versus timeshowing a low frequency respiratory component of the blood pressure.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In the following detailed description of the preferred embodiments,reference is made to the accompanying drawings which form a part hereof,and in which is shown by way of illustration specific embodiments inwhich the invention may be practiced. It is to be understood that otherembodiments may be utilized and structural or logical changes may bemade without departing from the scope of the present invention. Thefollowing detailed description, therefore, is not to be taken in alimiting sense, and the scope of the present invention is defined by theappended claims.

Referring to the block diagram of FIG. 1, there is indicated a pluralityof individual laboratory animals 10, 12 and 14 each having a bloodpressure sensor and telemetry transmitter of the type described in theBrockway U.S. Pat. No. 4,846,191 implanted therein. These implantedmodules are identified by numeral 11 in FIG. 1.

Disposed with or in proximity of each of the cages where the animals arekept is a telemetry receiver 15 which is tuned to pick up a signaltransmitted from an individual animal. The individual receivers, inturn, are connected to multiplexers, as at 16, capable of servicing thenumber of individual receivers connected thereto, whereby data from aparticular selected animal may be fed into the computer-based system 18for collecting, storing, displaying, and analyzing data from a largeplurality of animals.

In accordance with the present invention, the sensor/transmitters 11 aresurgically implanted within the animals so as to monitor blood pressurein a predetermined blood vessel. The sensor/transmitter transmits burstsof pulses, the timing of which codes the magnitude of the analog bloodpressure signal picked up by the sensor. Because the implanted unitsmeasure pressure relative to a vacuum, a pressure reference 20 is usedto provide an input of the ambient barometric pressure to thecomputer-based system 18. By subtracting the ambient room pressure fromthe transmitter pressure readings, changes in barometric pressure can beaccommodated.

Turning now to FIG. 2, there is illustrated by means of a software flowdiagram the algorithm executed by the computer-based system 18 forderiving both blood pressure information and respiratory informationfrom the blood pressure measurements taken using the equipmentillustrated in FIG. 1. This flow chart is in sufficient detail thatpersons skilled in programming an IBM PC or a clone thereof can writethe source code for such a computer.

The first step in the algorithm identified by numeral 20 is to bring inthe raw blood pressure data from an animal via the associated receiver15 and consolidation matrix 16. This data is temporarily held in a DMAbuffer (block 22) where it is maintained until called for by theprogram.

Had more than one sensor been implanted in the animal to providemeasurements of more than one physiologic parameter, such as, forexample, blood pressure and EKG, the data stream provided by theassociated telemetry transmitter would include both channels of data.Hence, the software includes a routine for separating the multichanneldata (block 24). In such an arrangement, a circular buffer is providedfor each of the parameters being measured so that data from theindividual channels can be separately stored (block 26). The data from acircular buffer, when selected, is processed in an interpolationalgorithm (block 28), which converts the data to points substantiallyequi-spaced in time. The interval between successive points is set bythe sample rate chosen in the software. It does so by fitting a thirdorder polynomial of the form y=ax³¹+bx²+cx +d to a series of four pointscomprising blood pressure readings at four different times. Continuingon with the assumption that it is the blood pressure parameter that hasbeen sensed and is being processed, at block 30, the data are convertedto appropriate units, e.g., mmHg. If noise is present in theinterpolated data, it may be necessary to low pass filter the data toremove high frequency noise (block 32).

The resulting waveform data may again be held in a buffer (block 34)until called for. If desired, and as represented by block 36, thewaveform can be saved on the computer's hard drive, a floppy-disk and/orpresented on a computer display screen. The blood pressure waveform canbe processed by a feature detection algorithm (block 38) in which thepeaks, valleys, slopes, zero-crossings and the like are examined toextract information of value to the researcher, such as systole,diastole, heart rate and dP/dt. Referring to the waveform of FIG. 3,there is illustrated a plot of blood pressure measured in mmHg versustime for a five-second interval. The systolic points obtained as aresult of the feature detection operation 38 are identified in FIG. 3 bynumeral 40 and the diastolic valleys by numeral 42. The systolic pointsand diastolic points shown in FIG. 3 are illustrative of sequences ofselected blood pressure features such as beat-to-beat systolic datapoints and beat-to-beat diastolic data points, but which can alsoinclude other blood pressure features such as beat-to-beat mean valuesof blood pressure over a predetermined time interval.

To obtain readings of the systolic and diastolic blood pressure, thepoints 40 and 42 may be averaged over a predetermined time interval suchas, for example, 10 seconds which, in FIG. 2, is referred to asparameter extraction (block 44). Control loops back, via path 46, to theinput of block 20 where further raw data telemetered from the implantedsensor or sensors is inputted for processing.

The algorithm represented by blocks 20 through 38 and 44 have been usedin the past for deriving blood pressure parameters on an on-line andoff-line basis. The present invention is concerned with the improvementwhereby respiratory parameters may also be derived from the measuredblood pressure signals obtained from the laboratory animals oralternatively from humans.

Referring again to FIG. 2, the series of systole points 40 obtained as aresult of the feature detection operation 38 are supplied as inputs toanother curve-fitting algorithm (block 48) which functions to addadditional points between the peaks 40, thereby creating a smooth curvebetween adjacent systolic peaks in the blood pressure versus timewaveform. The thus curve-fitted systolic waveform is labeled as such inFIG. 3. Once a third order curve has been fit to the data, the resultingwaveform is tested for critical points based on a predetermined criteria(block 50). For example, the predetermined criteria in the preferredembodiment defines critical points at maximum excursions above azero-crossing and/or peaks and valleys in the curve-fitted waveform. Atest is made at decision block 52 whether a critical point has beenreached and, if not, control exits via path 54 and further systolepoints are subjected to the curve-fitting algorithm at block 48.

When the test at decision block 52 indicates that a critical point hasbeen reached, the operation performed at block 56 determines whether thecritical point is a maximum or a minimum. By computing the intervalbetween two adjacent maximums or two adjacent minimums, the length of arespiratory cycle is obtained. The inverse of this cycle length isrespiratory rate, measured in breaths per second. The interval iscontinuously computed as represented by block 58 to provide a current,real-time indication of respiration rate. Although respiratory rate is aparameter of value and is the parameter derived in the preferredembodiment, the present invention is not limited to deriving respiratoryrate from the curve-fit beat-beat data as the present invention can beapplied to derive other physiologic parameters from the curve-fitbeat-beat data.

It is seen that there is provided a method and apparatus to deriverespiration rate and other physiologic parameters, either on-line oroff-line from a continuous blood pressure signal. This is accomplishedby way of a feature detection software algorithm. The capability ofcontinuous waveform processing provides useful data relating to therespiratory system. In addition to on-line processing, the same pressurewaveforms can be post-processed to derive respiration rate, otherrespiratory data, or other information related to other physiologicparameters which may be contained in the blood pressure waveform. Theinvention offers the advantage of obtaining data on more than onephysiologic parameter, e.g., blood pressure and respiratory rate, usingonly a single sensor implanted in the animal.

This invention has been described herein in considerable detail in orderto comply with the Patent Statutes and to provide those skilled in theart with the information needed to apply the novel principles and toconstruct and use such specialized components as are required. However,it is to be understood that the invention can be carried out byspecifically different equipment and devices, and that variousmodifications, both as to the equipment details and operatingprocedures, can be accomplished without departing from the scope of theinvention itself. For example, the present invention is not limited tothird order polynomials curves, as other n^(th) order polynomials andother suitable mathematical models can be similarly fitted to bloodpressure/time points according to the present invention. Likewise, it isnot necessary that the blood pressure data be telemetered. A bloodpressure sensor could, for example, transmit a signal indicative ofblood pressure via LEDs or wires to an amplifier and analog-to-digitalconverter, which provides a blood pressure signal into thecomputer-based system according to the present invention.

When considering modifications to the preferred embodiment, it is to beunderstood that the respiratory-related information is obtainable byperforming peak detection directly on the feature data without curvefitting, but since the data are not always ideal or equally spaced, itis difficult to resolve maximum and minimum points accurately asresolved by the present invention. Respiratory-related information isalso obtainable by performing spectral analysis on the raw pressurewaveform, but since the pressure data varies in frequency and amplitude,this approach is less than ideal in that it works best on truly periodicdata. One could also signal process the data in accordance with theBarthelmes paper cited in the background section in which the raw bloodpressure date is first high-pass filtered and then low-pass filtered.The Barthelmes approach, however, unlike the present invention, requiresan optimal design of the filter and amplifier characteristics, be theydigital or analog, to deal with a wide spectrum of data characteristics.

As to alternatives to the above described preferred embodiment, oneembodiment of the present invention performs spectral analysis on thecurve fit data values, such as the third order fitted curve, instead ofperforming the peak detection described above. Another embodiment of thepresent invention may achieve a more accurate indication of therespiratory effect on blood pressure by curve fitting the averagedsystolic and diastolic values for each cardiac cycle before applying apeak detection to determine respiration rate. This approach isadvantageous only when the systolic and diastolic curves remaincompletely in phase.

Although specific embodiments have been illustrated and described hereinfor purposes of description of the preferred embodiment, it will beappreciated by those of ordinary skill in the art that a wide variety ofalternate and/or equivalent implementations calculated to achieve thesame purposes may be substituted for the specific embodiments shown anddescribed without departing from the scope of the present invention.Those with skill in the mechanical, electro-mechanical, electrical, andcomputer arts will readily appreciate that the present invention may beimplemented in a very wide variety of embodiments. This application isintended to cover any adaptations or variations of the preferredembodiments discussed herein. Therefore, it is manifestly intended thatthis invention be limited only by the claims and the equivalentsthereof.

What is claimed is:
 1. A method comprising: obtaining a time-varyingblood pressure signal; extracting a sequence of blood pressure featuresfrom the blood pressure signal, the blood pressure features includingone of systolic points and diastolic points; curve-fitting to theextracted sequence of selected blood pressure features to yield a fittedsignal including respiration information; and obtaining respiration fromthe fitted signal.
 2. The method of claim 1, wherein the curve-fittinguses an n^(th) order polynominal curve.
 3. The method of claim 2,wherein n is at least equal to
 3. 4. The method of claim 1, wherein thesequence of blood pressure features corresponds to a sequence of cardiaccycles.
 5. The method of claim 1, wherein the extracted sequence ofblood pressure features, used by the curve-fitting, is substantiallyequal-spaced in time.
 6. The method of claim 1, wherein the obtainingrespiration information comprises computing an indicator of at least oneof respiration rate and respiration volume based on at least one of peakvalues, trough values, and zero-crossings of the fitted signal.
 7. Themethod of claim 1, in which obtaining the time-varying blood pressuresignal is performed within a human or animal, and further includingtransmitting a responsive signal carrying blood pressure informationfrom the human or animal for performing the extracting the sequence ofblood pressure features, the curve-fitting to the extracted sequence ofblood pressure features, and the obtaining respiration information fromthe fitted signal.
 8. The method of claim 7, further comprisingimplanting a blood pressure sensor in the human or animal.
 9. The methodof claim 1, in which at least one of the extracting the sequence ofblood pressure features, the curve-fitting to the extracted sequence ofblood pressure features, and the obtaining respiration information fromthe fitted signal includes digital processing of a signal.
 10. Themethod of claim 1, in which the obtaining respiration informationincludes performing spectral analysis on the fitted signal.
 11. Ansystem including: a blood pressure signal input, receiving a bloodpressure signal; a peak detector, configured to extracting a sequence ofblood pressure features from the blood pressure signal, the bloodpressure features including one of systolic points and diastolic points;a curve-fitting module, configured curve-fit to the extracted sequenceof selected blood pressure features to yield a fitted signal includingrespiration information; and a feature detector, including at least oneof a peak detector and a zero-cross detector, configured to obtainrespiration information from the fitted signal.
 12. The system of claim11, in which the curve-fitting module includes an n^(th) orderpolynomial curve.
 13. The system of claim 12, wherein n is at leastequal to
 3. 14. The system of claim 11, further including a timedifference circuit, coupled to an output of at least one of the peakdetector and the zero-cross detector, to determine a respiration periodtherefrom.
 15. The system of claim 11, further comprising a bloodpressure sensor.
 16. The system of claim 15, further comprising atransmitter, coupled to an output of the blood pressure sensor,configured to transmit a signal including blood pressure informationfrom within a human or animal.
 17. The system of claim 16, furtherincluding a receiver, configured to be communicatively coupled to thetransmitter to receive the transmitted signal including blood pressureinformation.
 18. The system of claim 11, including a digital signalprocessor that includes at least one of the peak detector, thecurve-fitting module, and the feature detector.
 19. The system of claim11, in which the feature detector includes a spectral analyzer forperforming spectral analysis on the fitted signal.